11-2131311-C-T

Variant names:

• chr11-2131311-C-T
• rs3168310
• NM_000612.6:c.*1676G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000612.6(IGF2):​c.*1676G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 233,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: IGF2 NM_000612.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910
• Publications: 11 publications found

Genes affected

IGF2 (HGNC:5466): (insulin like growth factor 2) This gene encodes a member of the insulin family of polypeptide growth factors, which are involved in development and growth. It is an imprinted gene, expressed only from the paternal allele, and epigenetic changes at this locus are associated with Wilms tumour, Beckwith-Wiedemann syndrome, rhabdomyosarcoma, and Silver-Russell syndrome. A read-through INS-IGF2 gene exists, whose 5' region overlaps the INS gene and the 3' region overlaps this gene. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2010]

INS-IGF2 (HGNC:33527): (INS-IGF2 readthrough) This locus includes two alternatively spliced read-through transcript variants which align to the INS gene in the 5' region and to the IGF2 gene in the 3' region. One transcript is predicted to encode a protein which shares the N-terminus with the INS protein but has a distinct and longer C-terminus, whereas the other transcript is a candidate for nonsense-mediated decay (NMD). The transcripts are imprinted and are paternally expressed in the limb and eye. [provided by RefSeq, Jul 2008]

ENSG00000284779 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS2: High AC in GnomAd4 at 12 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000612.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2	NM_000612.6	MANE Select	c.*1676G>A		3_prime_UTR	Exon 4 of 4	NP_000603.1
	INS-IGF2	NR_003512.4		n.2933G>A		non_coding_transcript_exon	Exon 7 of 7
	IGF2	NM_001127598.3		c.*1676G>A		3_prime_UTR	Exon 5 of 5	NP_001121070.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2	ENST00000416167.7	TSL:1 MANE Select	c.*1676G>A		3_prime_UTR	Exon 4 of 4	ENSP00000414497.2
	IGF2	ENST00000381406.8	TSL:2	c.*1676G>A		3_prime_UTR	Exon 4 of 4	ENSP00000370813.4
	IGF2	ENST00000381395.5	TSL:2	c.*1676G>A		3_prime_UTR	Exon 4 of 4	ENSP00000370802.1

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152144 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000148 AC: 12 AN: 81010 Hom.: 0 Cov.: 0 AF XY: 0.000134 AC XY: 5 AN XY: 37248

African (AFR) AF: 0.00 AC: 0 AN: 3892

American (AMR) AF: 0.00 AC: 0 AN: 2498

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5114

East Asian (EAS) AF: 0.000438 AC: 5 AN: 11408

South Asian (SAS) AF: 0.00 AC: 0 AN: 706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 68

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 492

European-Non Finnish (NFE) AF: 0.000140 AC: 7 AN: 50054

Other (OTH) AF: 0.00 AC: 0 AN: 6778

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152262 Hom.: 0 Cov.: 34 AF XY: 0.0000537 AC XY: 4 AN XY: 74430

African (AFR) AF: 0.0000241 AC: 1 AN: 41564

American (AMR) AF: 0.000261 AC: 4 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000388 AC: 2 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 1875

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.0
DANN	Benign	0.89
PhyloP100		-0.091
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3168310; hg19: chr11-2152541;